Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial (2023)

Type of publication:
Journal article

Joharatnam-Hogan N.; Hatem D.; Cafferty F.H.; Petrucci G.; Cameron D.A.; Ring A.; Kynaston H.G.; Gilbert D.C.; Wilson R.H.; Hubner R.A.; Swinson D.E.B.; Cleary S.; Robbins A.; MacKenzie M.; Scott-Brown M.W.G.; Sothi S.; Dawson L.K.; Capaldi L.M.; Churn M.; Cunningham D.; Khoo V.; Armstrong A.C.; Ainsworth N.L.; Horan G.; Wheatley D.A.; Mullen R.; Lofts F.J.; Walther A.; Herbertson R.A.; Eaton J.D.; O'Callaghan A.; Eichholz A.; Kagzi M.M.; Patterson D.M.; Narahari K.; Bradbury J.; Stokes Z.; Rizvi A.J.; Walker G.A.; Kunene V.L.; *Srihari N.; Gentry-Maharaj A.; Meade A.; Patrono C.; Rocca B.; Langley R.E.

British Journal of Cancer. 129(4):706-720, 2023 Sep.

Background: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. Method(s): Urinary 11-dehydro-thromboxane B2(U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. Result(s): In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. Conclusion(s): Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.

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